Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat.
Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat.
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DOI：
10.1016/j.neuroscience.2012.08.058
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发表时间：
2012-12-06
期刊：
影响因子：
3.3
通讯作者：
Lifshitz, J.
中科院分区：
文献类型：
--
作者：
Cao, T.;Thomas, T. C.;Ziebell, J. M.;Pauly, J. R.;Lifshitz, J.
Traumatic brain injury (TBI) survivors experience long-term post-traumatic morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to whisker stimulation models the agitation of TBI survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate post-traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here we hypothesize that a temporal sequence of microglial activation states contributes to the circuit pathology responsible for post-traumatic morbidity, and test the hypothesis by examining microglial morphological activation and neuroinflammatory markers for activation states through gene expression and receptor binding affinity. Adult male, Sprague-Dawley rats were subjected to a single moderate midline fluid percussion (FPI) or sham injury. Microglial activation was determined by immunohistochemistry, quantitative real-time PCR and receptor autoradiography in the primary somatosensory barrel field (S1BF) and ventral posteromedial nucleus of the thalamus (VPM) at 7 and 28 days following FPI. Morphological changes indicative of microglial activation, including swollen cell body with thicker, shrunken processes, were evident in S1BF and VPM at 7 and 28 days post-injury. Principally at 7 days post-injury in VPM, general inflammatory gene expression (MHC-I, MHC-II, translocator protein 18 kDa [TSPO]) is increased above sham level and TSPO gene expression confirmed by receptor autoradiography. Further, CD45, a marker of classical activation, and TGF-βI, an acquired deactivation marker, were elevated significantly above sham at 7 days post-injury. Daily administration of the anti-inflammatory ibuprofen (20 mg/kg, i.p.) significantly reduced the expression of these genes. Evidence for alternative activation (arginase 1) was not observed. Thus, these data demonstrate concomitant classical activation and acquired deactivation phenotypes of microglia in diffuse TBI in the absence of overt contusion or cavitation. Anti-inflammatory treatment may further alleviate the neuropathological burden of post-traumatic inflammation.
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影响因子：
--
作者：
Cullheim, Staffan;Thams, Sebastian
通讯作者：
Thams, Sebastian
影响因子：
6.4
作者：
GRAHAM, DI;ADAMS, JH;GENNARELLI, TA
通讯作者：
GENNARELLI, TA
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
影响因子：
2.9
作者：
Hall, Kelley D.;Lifshitz, Jonathan
通讯作者：
Lifshitz, Jonathan
DOI：
10.1249/mss.0b013e31819fcd1b
发表时间：
2009-09-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Hosseini, Ario H.;Lifshitz, Jonathan
通讯作者：
Lifshitz, Jonathan